Spreading-dependent or independent Sir2-mediated gene silencing in budding yeast

In the budding yeast Saccharomyces cerevisiae, a silent chromatin structure is formed at three distinct loci, including telomeres, rDNA, and mating-type loci, which silence the expression of genes within their structures. Sir2 is the only common factor, regulating the three silent chromatin regions. S. cerevisiae has 32 telomeres, but studies on gene silencing in budding yeast have been performed using some reporter genes, artificially inserted in the telomeric regions. Therefore, insights into the global landscape of Sir-dependent silencing of genes within the silent chromatin regions are required.

This study aimed to obtain global insights into Sir2-dependent gene silencing on all silent chromatin regions in budding yeast.

RNA-sequencing was performed to identify genes that are silenced by Sir2. By comparing with the chromatin immunoprecipitation-sequencing (ChIP-seq) of Sir2 in the wild-type strain, we confirmed Sir2-regulated genes.

Using Sir2 ChIP-seq data, we identified that the Sir2 binding domain length caused by Sir2 spreading from the chromosomal end is different in each telomere in budding yeast. Expression of most subtelomeric genes increased in the ∆sir2 strain. Some Sir2-regulated subtelomeric genes were positioned within the telomeric Sir2-binding domain, while the others were outside the Sir2-binding domain. In addition, Sir2 was bound to the mating-type loci and rDNA region, and gene expression increased in the ∆sir2 strain.

We concluded that S. cerevisiae has two modes of Sir2-mediated gene silencing: one is dependent on chromatin binding and spreading of Sir2, and the other is independent of spreading of Sir2.